This particular area of research is indispensable to understanding genetic and infectious diseases as well as cancer. Without the strict control of gene expression, organisms would not develop properly or be able to sustain life. The goal of this research project is aimed at defining the function of a newly discovered epigenetic DNA marker involving DNA methylation at symmetric CCWGG (i.e., CCWGG, W = A/T) sites, in regulating B cell gene expression in normal development. Gene silencing involves chromatin and DNA modifications that impose a higher order of repression that supersedes trans-acting transcription factor function. Silenced genes are well known to have dense CpG methylation and extensive histone deacetylation. However, the mechanisms and modifications in DNA and chromatin structure that lead to these modifications and subsequent gene silencing are just now being resolved. This application on developmental B cell gene control is aimed at determining the role of DNA methylation recently discovered at CCWGG sites in turning off established patterns of gene expression during key transitions in normal B cell development and during the initiation of the chromatin modifications involved in gene silencing. State-of-the-art molecular biology techniques including genomic bisulfite sequencing and chromatin immunoprecipitation will be used to accomplish the proposed program. The study of gene regulation is a fundamental part of the search for more effective treatments for a wide range of diseases including heart disease, diabetes, autoimmune disorders, and cancer. Controlling when and where all genes are turned on and off is critical for normal cell function. The goal of this research project is to understand the developmental control of white blood cell-specific genes, which when properly turned on allow white blood cells to develop into infectious disease-fighting cells. The study of gene regulation is a fundamental part of the search for more effective treatments for a wide range of diseases including heart disease, diabetes, autoimmune disorders, and cancer. [unreadable] [unreadable] [unreadable]